Inflammatory responses induced by poly-l-arginine in rat lungsin vivo

Agents and Actions - 1993
A. Santana1, S. Hyslop1, E. Antunes1, M. Mariano2, Y. S. Bakhle3, G. de Nucci1
1Department of Pharmacology, Faculty of Medical Sciences, UNICAMP, Campinas, Brazil
2Department of Immunology, Institute of Biomedical Sciences USP, São Paulo, Brazil
3Royal College of Surgeons, London, UK

Tóm tắt

The inflammatory responses induced by the synthetic polycation poly-l-arginine injected either into the pleural cavity or into the trachea in rats have been investigated. Poly-l-arginine (4–40 nmol/rat) injected intrapleurally induced exudate formation and leucocyte migration (mainly polymorphonuclear cells). The exudate formation (but not cell migration) was dependent on the molecular weight of the poly-l-arginine used (24 and 115 kD). The poly-l-arginine-induced pleurisy was mainly dependent on activation of mast cells since it was significantly reduced either in rats depleted of their stores of histamine and serotonin or in rats previously treated with the serotonin receptor antagonist methysergide. The polyanions heparin and dermatan sulphate when administered intrapleurally with the polycation markedly reduced the exudate formation. Poly-l-arginine (115 kD, 8.5 nmol/rat) injected intratracheally caused lung oedema, increased leucocyte number and protein content of bronchoalveolar lavage, respiratory insufficiency and 60% mortality in 6 h. Depletion of histamine and serotonin stores or of circulating neutrophils decreased the leucocytes in bronchoalveolar lavage but did not increase survival rate, whereas the polyanion dermatan sulphate prevented the mortality completely. These results suggest that the inflammatory changes caused by poly-l-arginine are dependent on mast cell activation but that the lethality after intratracheal administration is due to electrostatic interactions of the polycation with anionic surfaces present in the pulmonary epithelium.

Từ khóa


Tài liệu tham khảo

O. Stein, A. De Vries and E. Katchalski,The effect of polyamino acids on the blood vessels of the rat. Arch. Int. Pharmacodyn.57, 243–253 (1956).

L. Needham, P. G. Hellewell, T. J. Williams and J. L. Gordon,Endothelial functional responses and increased vascular permeability induced by polycations. Lab. Invest.59, 538–548 (1988).

E. Antunes, M. Mariano, G. Cirino, S. Levi and G. de Nucci,Pharmacological characterization of polycation-induced rat hind-paw oedema. Br. J. Pharmacol.101, 986–990 (1990).

J. Padawer,The reaction of rat mast cells to polylysine. J. Cell Biol. 352–372 (1970).

M. Ennis, F. L. Pearce and P. M. Westton,Some studies on the release of histamine from mast cells stimulated with polylysine. Br. J. Pharmacol.70, 329–334 (1980).

O. H. Lowry, N. J. Rosebrough, A. L. Farr and A. J. Randall,Protein measurement with the folin phenol reagent. J. Biol. Chem.193, 265–275 (1951).

M. Di Rosa, J. P. Giroud and D. A. Willoughby,Studies of the mediators of the acute inflammatory response induced in rats in different sites by carrageenan and turpentine. J. Pathol.104, 15–29 (1971).

W. G. Spector and D. A. Willoughby,The demonstration of the role of mediators in turpentine pleurisy in rats by experimental suppression of the inflammatory changes. J. Pathol. Bact.77, 1–17 (1959).

T. Suzuki-Nishimura, H. Sekino, Y. Yoshino, K. Nagaya, N. Oku, N. Nango and M. K. Uchida,Synthetic polycations, polyethylenimines and polyallylamines release histamine from rat mast cells. Jpn. J. Pharmacol.51, 279–290 (1989).

G. de Nucci, J. A. Salmon and S. Moncada,Anaphylaxis in guinea pig isolated lungs perfused via the trachea. Eur. J. Pharmacol.130, 249–256 (1986).

V. Lagente, S. Moncade, G. de Nucci and Payne A,Aerosol sensitization of guinea-pigs: Effect of paraquat. Br. J. Pharmacol.90, 35p (1987).

E. Skultelsky, Z. Rudich and D. Danon,Surface charge properties of the luminal front of blood vessel wall: An electron microscopical analysis. Thromb. Res.7, 623–634 (1975).

E. Skultelsky and D. Danon,Redistribution of surface anionic site on the luminal front of blood vessel endothelium after interaction with polycationic ligand. J. Cell. Biol.71, 232–241 (1976).

M. Simionescu, N. Simionescu, J. E. Silbert and G. E. Palade,Differentiated microdomains on the luminal surface of the capillary endothelium: II. Partial characterization of their anionic sites. J. Cell Biol.90, 614–621 (1981).

J. L. Barnes, R. A. Radnik, E. P. Gilchrist and M. A. Venkatachalam,Size and charge selective permeability defects induced in glomerular basement membrane by a polycation. Kidney Int.25, 11–19 (1984).

S. J. Lai-Fook and L. V. Brown,Effects of electric charge on hydraulic conductivity of pulmonary interstitium. J. Appl. Physiol.70, 1928–1932 (1991).

R. L. Barker, R. H. Gundel, G. J. Gleich, J. L. Checkel, D. A. Loegering, L. R. Pease and K. J. Hamann,Acidic polyamino acids inhibit human eosinophil granule major basic protein toxicity. J. Clin. Invest.88, 798–805 (1991).

K. Fredens, R. Dahl and P. Venge,In vitro studies of the interaction between heparin and eosinophil cationic protein. Allergy46, 27–29 (1991).

Thông tin
Thông tin xuất bản

Agents and Actions

Thông tin tác giả